The configuration at the α-position is less predictable, especially in cases when epimerization can occur. On the basis of steric approach control, the new α-substituent is predicted to be trans to the new β-substituent, and this is observed in a number of cases. (3) Scope and limitations Nucleophiles and electrophiles Organocopper reagents are the most common nucleophiles for the β-addition step. These reagents can be generated catalytically in the presence of Grignard reagents using either copper(I) or copper(II) salts. (4)Copper reagents can also be used stoichiometrically, and among these, organocuprates are the most common (they are more reactive than the corresponding neutral organocopper(I) compounds). The cuprate counterion may affect the addition and subsequent enolate reaction in subtle ways. Additions involving higher-order cuprates must be quenched with a silyl halide before alkylation. (5) When unsymmetrical cuprates are employed, the group whose carbon-copper bond contains less s character is almost always transferred to the β-position. A few exceptions exist, however. In the example below, conducting the reaction in THF led to transfer of the vinyl moiety, while other solvents promoted methyl transfer. (6) Enolates can also be used as nucleophiles for vicinal difunctionalization reactions. To prevent simple Michael addition (which culminates in protonation of the enolate intermediate), trapping by the electrophile must be intramolecular. (7) Considerations of the electrophile should take into account the nature of the conjugate enolate generated after the first step. Relatively reactive alkylating agents should be used, especially in cases involving the addition of cuprates (enolates resulting from the addition of cuprates are often unreactive). Oxophilic electrophiles should be avoided, if C-alkylation is desired. Electrophiles should also lack hydrogens acidic enough to be deprotonated by an enolate. α,β-Unsaturated carbonyl compounds Cyclic α,β-unsaturated ketones are the most commonly employed substrates for vicinal difunctionalization. They tend to be more reactive than acyclic analogues and undergo less direct addition than aldehydes. Amides and esters can be used to encourage conjugate addition in cases when direct addition may be competitive (as in the addition of organolithium compounds). (8) Because the addition step is highly sensitive to steric effects, β-substituents are likely to slow the reaction. Acetylenic and allenic substrates react to give products with some retained unsaturation. (9) Synthetic applications A large number of examples of vicinal difunctionalization of unsaturated carbonyl compounds exist in the literature. In one example, the difunctionalization of unsaturated lactone 1 was employed en route to isostegane. This